The Roles of TRAF3 in Immune Responses

Figure 2

Engagement of Toll-like receptor (TLR) and retinoic acid-induced gene-1 like receptor (RLR) triggers two main signaling pathways that are dependent on either myeloid differentiation primary response protein 88 (MYD88) or TIR domain-containing adaptor protein inducing IFNβ (TRIF). TNFR-associated factor 3 (TRAF3) is recruited to both the MYD88-assembled and TRIF-assembled signaling complexes which upregulate IRF3 and IRF7 activation, depending on the catalytic activity of TANK-binding kinase1 (TBK1) and the IκB kinaseε (IKKε). TRAF6 is essential for activating most known MYD88-dependent effector pathways, including the nuclear factor-κB (NF-κB). The classical NF-κB pathway, which is triggered by RLRs, Toll-like receptors (TLRs), and TNF receptors (TNFRs), depends on the catalytic activity of the IκB kinase (IKK) catalytic subunit IKKα and IKKβ. The nonclassical NF-κB pathway is mainly activated by a subset of TNFR and depends on the catalytic activity of IKKα, which is activated by NF-κB-inducing kinase (NIK), the turnover of which is regulated by TRAF3. Activated IKKα phosphorylates p100, freeing its N-terminal portion (p52), which enters the nucleus together with RELB.